Phase II Study of Short Course FOLFOX Chemotherapy With Either Nivolumab or Nivolumab + Radiation in the First Line Treatment of Metastatic or Unresectable Gastroesophageal Cancers (BMS Protocol CA209-76L)

Gastroesophageal Adenocarcinoma Clinical Trial

Official title:

Phase II Study of Short Course FOLFOX Chemotherapy With Either Nivolumab or Nivolumab + Radiation in the First Line Treatment of Metastatic or Unresectable Gastroesophageal Cancers (BMS Protocol CA209-76L)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04021108
• Other study ID #: 1812019872
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 22, 2019
• Est. completion date: April 2026

Study information

• Verified date: January 2024
• Source: Weill Medical College of Cornell University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized phase II study examining nivolumab alone versus radiation therapy with nivolumab in subjects who did not have disease progression to initial therapy with the combination of FOLFOX and Nivolumab.

Description:

This is a randomized phase II study examining nivolumab alone versus radiation therapy with nivolumab in subjects who did not have disease progression to initial therapy with the combination of FOLFOX and Nivolumab. Subjects with advanced unresectable or metastatic gastroesophageal adenocarcinoma are eligible. All subjects will receive FOLFOX + nivolumab therapy. Subjects who demonstrate at least stable disease, as per RECIST 1.1, on their first imaging assessment at two months will receive one additional month of FOLFOX + nivolumab (3 months total), and then will be randomly assigned at a 1:1 ratio to receive either nivolumab alone or nivolumab plus radiation therapy. Radiation therapy fields and technique will be approved by central review. Radiation will be planned at 4Gy x 5 doses (20 Gy total), given concurrently with nivolumab. After 4 months of therapy, patients who remain on study will receive nivolumab 480 mg every 4 weeks. Subjects will be on study (intervention + follow-up) for approximately 24 months. The projected end date of the study, including data analysis, is February 2026.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: April 2026
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Subjects with a diagnosis of advanced unresectable or metastatic gastroesophageal adenocarcinoma (eg. gastric, gastroesophageal junction, and esophageal adenocarcinoma)
• Be willing and able to provide written informed consent/assent for the trial
• Age > 18 years
• ECOG performance status = 1
• Absolute neutrophil count = 1,500/mL
• Platelets = 100,000/mL
• Total bilirubin = 1.5x upper limits of normal, unless the patient has known Gilbert's disease.
• AST/ALT = 2.5 upper limits of normal, or < 5x ULN for subjects with liver metastases
• Creatinine = 1.5 mg/dl. If Creatinine > 1.5 mg/dl, creatinine clearance > 60 ml/min
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 28 days prior to initiation of treatment on Day 1.
• For all males and females of childbearing potential, they should be agreeable to use an adequate method of contraception or birth control. For females of child bearing potential, a negative pregnancy test within 7 days of start of study drug is required Exclusion Criteria
• Prior cytotoxic therapy for metastatic or incurable disease.
• Patients may have had prior therapy with curative intent for localized disease, if their recurrence or disease progression was more than six months from completing prior therapy.
• HER2 positive adenocarcinoma
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Known history of active TB (Bacillus Tuberculosis)
• Known additional malignancy that is active. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Previous invasive malignancy treated with curative intent less than 3 years from time of registration. Exceptions include prostate cancer or basal cell skin cancer.
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Known history of, or any evidence of active, non-infectious pneumonitis.
• Active infection requiring systemic therapy.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
• Has received a live vaccine within 30 days of planned start of study therapy.

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastroesophageal Adenocarcinoma

Intervention

Drug:
• Nivolumab 240 MG
Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.

Locations

Country	Name	City	State
United States	Roswell Park Cancer Center	Buffalo	New York
United States	Weill Cornell Medicine	New York	New York
United States	University of Nebraska	Omaha	Nebraska
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Weill Medical College of Cornell University	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with 12-month progression free survival	This will be measured by number of patients without disease progression at 12 months in the two study arms (patients who receive nivolumab with radiation and those who receive nivolumab alone)	12 months
Secondary	Number of subjects who receive short course chemotherapy with immunotherapy that achieve 12-month progression free survival	This will be measured by the number of patients without disease progression at 12 months in all enrolled patients.	12 months
Secondary	Overall Survival, as measured by the rate of survival in patients	In both study arms, and in all patients together, we will examine the rate of survival in patients over time from registration through their treatment	2 year
Secondary	Occurrence of Significant Toxicity, as measured by Number of Grade 3 and Grade 4 Adverse Events (Combined) Attributable to Immunotherapy	We will measure the rate of grade 3 or 4 adverse events attributable to immunotherapy in both study arms	2 year